Solid tumors require their own vascular supply (neoangiogenesis) for growth, since the supply of nutrients and oxygen by diffusion is insufficient from a certain size. Neoangiogenesis is mediated, inter alia, by osteopontin (OPN), which is secreted at an early stage by aggressive primary tumors and also, as the case may be, by metastasizing tumor cells. OPN causes bone marrow cells which are still undifferentiated and/or more differentiated to migrate from the bone to the metastasizing loci. There the precursor cells differentiate and form a tumor stroma which promotes further tumor growth, and colonization and also neoangiogenesis. Up to 30% of the cellular portion of primary tumors or metastases may originate from these recruited bone marrow cells, which can multiply at the site by further dividing growth before they finally differentiate.
WO 2005/072780 describes reagents and formulations for the ex vivo labeling of cells, with the aim of providing these cells for an imaging technique (MRI, MRS). Preference is given to using fluorocarbon-based imaging reagents for the labeling. There is described a multiplicity of cells which can be labeled and used in a multiplicity of clinical methods.
WO 00/71169 describes the use of MR-sensitive contrast agents for treating living cells in order to be able to provide these cells for MR imaging. The cells thus labeled may be used for diagnostic or therapeutic purposes or for research purposes. The methods and reagents described in this communication are suitable for the labeling of a multiplicity of cells.
S. A. Anderson et al. describe in Blood, vol. 105, no. 1 (2005), pages 420-425, a noninvasive imaging of magnetically labeled stem cells in order to study new vascular formation in a glioma model. The labeling method of this communication is suitable for the monitoring of tumor growth, for the monitoring of the gene therapy for tumors, and also for the monitoring of the therapeutic transplantation of endothelial precursor cells for neovascularization in the case of a brain or heart infarct.
No references to a diagnosis of metastasizing tumors can be found in the prior art.
Metastases are often diagnosed late, since a certain cell number has to be reached before detection is feasible. In most cases, the metastases have already become further advanced and symptomatic at this point, and a curative therapy for metastasizing tumors is therefore no longer possible.
With the methods of the prior art, metastases can only be diagnosed from a certain size. This is achieved, for example, by FDG-PET. Alternatively, for certain tumors, chemotherapy is delivered prophylactically in order to destroy any metastases present. Overall, however, all approaches of the prior art are unsatisfactory for a timely diagnosis or for overcoming the problem of late diagnosis options for metastases.